Folding Forum

I've recruited my son's PC to help with covid-19, but I really can't explain what it is doing. Can somebody dumb it down for me?

Also how many atoms are in the spike? How many spikes are on a single SARS-CoV-2 virion? How many atoms does it take to make one of these virons? We really have no idea what kind of scale we're dealing with.

Welcome to the F@H Forum dana44,

I suggest reading this article and watching the videos. While there is technical jargon in the article, the videos themselves are less technical which may help you understand what's happening: https://foldingathome.org/2020/05/28/th ... -moonshot/

I can try to explain the computing, but you mostly seem to want to know about the biochemistry and the medicine. I am not able to help there.

One type of computer processor is called SIMD, where a Single Instruction is performed on Multiple sets of Data. This is useful to F@H as they have thousands of atoms in a Protein and each atom may have multiple bonds. Carbon likes 4 bonds.

Starting in 2001 Intel (and AMD by 2003) made a add on processor within the Pentium 4 called SSE2 that could perform 4 floating point adds or multiplies at the same time. As you might imagine, this made SSE2 four times faster than using the main Pentium 4. In 2011, Intel and AMD made a new SIMD engine called AVX_256 that does 8 Floating Point add or Multiplies at once, so at least twice the speed of SSE2.

(Intel added AVX_512 in 2013 for server CPUs, but they are not @Home CPUs, so F@H does not use them. (yet) Eventually AVX_512 offers another doubling of CPU power)

As CPUs get more threads, each has it's own SIMD engine, so modern CPUs may be able to do 256 threads of 8 floating point instructions at once. (16 threads is a lot more common)

Graphics cards had traditionally used fixed adders and multipliers to do math to make the graphics you can see. In 2006/2007 Nvidia and AMD (then ATI) started making graphics cards with generalized math units that could be programmed to whatever math the game needed. (Graphics cards are dominated by the needs of video games) At first these might have 16 to 48 math units (often called shaders or CUDA cores) which offered to do dozens of add or multiplies at once. Today a modern high end graphics card may have 5000 shaders, so can do a LOT of math, so long as you want to do the exact same math on 5000 pieces of data.

For larger Proteins, this is wonderful. You may notice owners of these cards whining if they get too small a Protein to analyze, as it can't keep all those shaders busy. CPUs do fine with the smaller proteins, much of the COVID-19 work is for CPUs. (I mention this only as a rumor, but some researchers will be more familiar with the programing in CPUs, called GROMACS, than with the programming in GPUs, called OpenMM. Do not discount ease of use)

So, because they need to do the exact same math for every bond in every atom in the molecule, F@H is very efficient at SIMD. Often folks will discover that nothing heats up their computer more than F@H, it is doing a lot of work.

And yet, the amount of work the Biochemist researchers need is even more massive. so they invite volunteers to donate computer time to solve how these Proteins fold. About 100,000 named individuals are donating computer time to solve COVID-19 and other diseases that involve folding and mis-folding Proteins. Some of us use more than one computer, and some fold anonymously, so the number of PCs folding is larger yet.

https://en.wikipedia.org/wiki/SIMD
https://en.wikipedia.org/wiki/SSE2
https://en.wikipedia.org/wiki/Advanced_ ... Extensions
https://en.wikipedia.org/wiki/General-p ... sing_units
https://en.wikipedia.org/wiki/GROMACS
https://en.wikipedia.org/wiki/Molecular ... ng_on_GPUs

Well I hope that helps, if not, I tried!

The appropriate explanation depends on the individual 12 year old concerned. Given the level of questions posed I would assume he's an intelligent lad, here are a couple of additional references that are most likely the appropriate level for anyone looking to learn about the science behind F@H. As for the specifics of COVID-19 spikes that is what the folding projects are trying to establish so they can develop something to combat it. Trouble is, it has already mutated since the first outbreak began and there is a second wave starting, possibly a third and more to follow. We could be living with new strains for decades.

https://foldingathome.org/diseases/
https://foldingathome.org/covid19/
https://en.wikipedia.org/wiki/Protein_folding

JimboPalmer wrote:...CPUs do fine with the smaller proteins, much of the COVID-19 work is for CPUs. (I mention this only as a rumor, but some researchers will be more familiar with the programing in CPUs, called GROMACS, than with the programming in GPUs, called OpenMM. Do not discount ease of use)...

CPUs and GPUs can both handle large number of atoms. However, the issue they encounter would be the same, i.e. large proteins on low-end system would struggle while high-end one would eat them for breakfast. Project 14236 & 14201 both have same number of 453,348 atoms and each one is for CPU and GPU.

I would say that there's a lot more GPUs than CPUs folding thus, the impression is that CPUs don't run out of WUs while the GPUs does. Thus, science on GPUs progresses a lot faster than CPU simply due to the sheer number and also speed.

The lack of GPU work units is probably in big part due to those huge datacenters which donated idle GPU resources to the project. Kind of a blessing and a curse at the same time

PantherX wrote:Project 14236 & 14201 both have same number of 453,348 atoms...

https://stats.foldingathome.org/project?p=14236 simply says

Coronavirus SARS-CoV-2 (COVID-19 causing virus) proteins.

These are high-priority projects to simulate the proteins of the COVID-19.

Do we know which proteins? All of them? Or just a part like the famous spike?

Unfortunately, I am not aware. The information published on the Project Description is all that I know. The blog post it links to could potentially indicate that it is related to the project that is mentioned in the blog post.

I don't in what way you can break down what your PC is doing in terms he would understand.
But presuming I had a 12 year old, I'd open up the Viewer.
He sees a string of dots dancing around on the screen.
You tell him those are atoms, they form a cluster, which forms cells. Could be part of a cancer, or part of a virus or whatever...
The cells, atom clusters, get bombarded with some sort of medicine, or other atoms, to see how it will react to it.
If in such case the bad cells (atoms) fall apart, you get a hit!
If nothing happens, you have a miss.
Hits are good.
Misses are waste of electricity and resources.
I would estimate we waste about 99.9% or more of our resources, just 'missing', hoping to get that one 'hit'.
That one 'hit' could mean the development of new medicine, or new applications on that cell.

All that is happening either in the graphics card, or CPU.
It is literally simulating in slow motion, the movements of these atoms.

I could be wrong, but that's the way I understand it.

I would suggest that in your analogy, the "miss" are not wasted, instead, they are valuable since we learn what not to do. In science, failures in experiments are valuable too, not just successful ones. The data from these experiments can help build a better foundational understanding that helps the scientific community.

NRT_AntiKytherA wrote:The appropriate explanation depends on the individual 12 year old concerned. Given the level of questions posed I would assume he's an intelligent lad, here are a couple of additional references that are most likely the appropriate level for anyone looking to learn about the science behind F@H. As for the specifics of COVID-19 spikes that is what the folding projects are trying to establish so they can develop something to combat it...

Thank you. He is curious. He has just started programming with Scratch. It's been a joy to watch him learn. "Look Dad, I figured out how to make gravity. My teacher didn't even know how! Just make wind that goes down!" So he's been able to simulate "gravity" and a few things jumping around in a world he made. He's obviously thinking ahead - instead of just one or two entities in a 2D world if he knew more he could make a 3D world down to the atom where things are simulated.

He knows the world is made of atoms and those make molecules. I'm learning certain molecules can make amino acids and a few of those can make peptides. And a few of those can make an entire protein? This long string of molecules is like a wire of a spring, it has a natural resting state. The resting state is determined by the pull of gravity by the individual atoms? If I remember my tinker toy chemistry classes atoms have "connection slots". e.g. hydrogen has one and oxygen has two. So you can have one oxygen connected to two hydrogen for water or two oxygen connected for something else? I forget/never fully understood how those work. How do these molecules connect to form amino acids and above? It's not using the atom connections, right? Otherwise that would just be called a bigger molecule? I really struggling myself to know how out world works.

Somehow all the above stuff leads to folding a protein to find how the atoms/molecules/proteins "want" to be, right? And then what do our computers simulate? A bunch of other groups of atoms as a drug interacting with one of these folded proteins? Like are we dealing with one spike or the entire thing?

Also he asked if a vaccine is just dead flu cells aren't there enough dead SARS-CoV-2 cells out now that we could inject them in to some people?

It's my understanding a virion isn't really alive or dead, it simply exists or not? Is it even correct to call it a cell? At this point I told him its a good idea and I'd try to look up why they can't just do that for him. Can anybody help, please?

dana44 wrote:...He knows the world is made of atoms and those make molecules. I'm learning certain molecules can make amino acids and a few of those can make peptides. And a few of those can make an entire protein? This long string of molecules is like a wire of a spring, it has a natural resting state. The resting state is determined by the pull of gravity by the individual atoms? If I remember my tinker toy chemistry classes atoms have "connection slots". e.g. hydrogen has one and oxygen has two. So you can have one oxygen connected to two hydrogen for water or two oxygen connected for something else? I forget/never fully understood how those work. How do these molecules connect to form amino acids and above? It's not using the atom connections, right? Otherwise that would just be called a bigger molecule? I really struggling myself to know how out world works...

That's a great start to know that the elemental building blocks consist of atoms (for sake of simplicity, any sub-atomic particles won't be considered since that isn't an element at that level). The human body uses only 21 amino acids to create the various proteins it needs (https://askabiologist.asu.edu/venom/bui ... ks-protein). Amino acids are the building blocks of peptides, proteins, enzymes, etc. (https://www.scientificpsychic.com/fitne ... acids.html). On an atomic level, gravity doesn't hold the atoms/molecules together (https://www.exploratorium.edu/origins/c ... dard2.html), it is the intramolecular and intermolecular forces (https://www.khanacademy.org/science/cla ... lar-forces).

...Somehow all the above stuff leads to folding a protein to find how the atoms/molecules/proteins "want" to be, right? And then what do our computers simulate? A bunch of other groups of atoms as a drug interacting with one of these folded proteins? Like are we dealing with one spike or the entire thing?

When proteins fold properly/correctly, everything is working fine as expected. However, when errors/mistakes occur, it is call misfolding which causes issues (https://www.sciencedaily.com/releases/2 ... 084627.htm). For F@H, we simulate the different ways a protein a protein can take to end up in a folded state (https://en.wikipedia.org/wiki/File:ACBP ... @home.tiff).

I don't know if I can add anything to this conversation, and I'm not a scientist, but here are some thoughts to what PantherX had to say:

PantherX wrote:For F@H, we simulate the different ways a protein a protein can take to end up in a folded state

Understanding the individual steps that a protein goes through along the way to becoming its final form might reveal weak spots in the protein that are not present in its final form. This could provide useful insights for attacking proteins in the SARS Corona virus that are not apparent when looking at the protein's final form. I've struggled with finding a suitable analogy for this. The closest I've come up with is that of hedgehog or a porcupine which rolls itself into a ball to protect itself from attack. Once it's balled up, it doesn't have many weak points. However, in the process of assuming it's final shape, it does expose weak spots. I think of proteins in viruses in the same way. Once they're completely formed, they might be hard to attack. As they fold themselves into their final shape, they may expose target areas that are not available once the folding is complete. I'm sure there are better analogies for this.

Here's a quote from Dr. Bowman in the REDDIT AMA that describes the concept:

"In a recent example from our lab, we designed drug-like molecules that target a cryptic pocket identified in our simulations (a pocket that is absent in available experimental structures but that we see form in our simulations). Then we experimentally confirmed that the compounds worked as intended."

I don't know how to link specifically to his comment, but the AMA is here https://www.reddit.com/r/pcmasterrace/c ... ronavirus/

I may have this wrong, but thought I'd give it a shot.

Nert wrote:...I don't know how to link specifically to his comment, but the AMA is here https://www.reddit.com/r/pcmasterrace/c ... ronavirus/...

Underneath comments, there's an option call "permalink" so when you click on it, it creates a link to that comment. In this case, this is the link: https://www.reddit.com/r/pcmasterrace/c ... s/fkzf153/